Basic and Translational Research Programs

Role of NETs and TRAPs in inflammatory loss ofcardiac function: Neutrophil Extracellular Traps (NETs) are web-like structures discovered by Volker Brinkmann and Arturo Zychlinsky in 2004, able to entrap bacteria, fungi, protozoa, and virus. They are extruded by activated neutrophils and are composed of DNA fibers, histones, and antimicrobial proteins in which pathogens are immobilized and exposed to a local high and lethal concentration of effector proteins.

Neutrophil Extracellular TRAPS (Nets) have been identified at sites of cardiac ischemic injury, but currently, the role of these TRAPs in heart disease and many other non-infectious pathology  has not been unraveled.

At sites of non-infectious tissue injury and inflammation, locally produced TRAPs from initially recruited leukocytes 1) trigger local cell activation and toxic cell death of productive pro-inflammatory and pro-fibrotic mediators, which ultimately results in loss of local tissue architecture and function (e.g., fibrosis). Identifying these TRAP induced pro-inflammatory/pro-fibrotic mediators and pathways in vitro will be the first step in designing and validating novel new therapies for TRAP-induced inflammation and tissue destruction in vivo.

In collaboration with Dr. Donald Kreutzer and Dr. Roshanak Sharafieh, our lab is actively working on identifying the role of Nets in heart failure, using in-vitro and in-vivo models. Identification of this interaction will aid in developing biomarkers for identifying cardiac injury and also has immense potential for therapeutic targets.

SARS-CoV-2: As we all know, COVID affects the lungs. However, it also affects the heart in all stages of the disease (mild, moderate, or severe) and more often in hospitalized and severely ill patients. In collaboration with the University of Tennessee Health Sciences Center, we aim to gain insights into the cardiac pathologies associated with SARS-COVID-19 infection and use a small animal model to study the disease process at a highly restricted biosafety laboratory. We have developed an animal model to understand the cardiac effects of the virus on the heart. In addition, this model helps in the development and testing of therapeutics and vaccines and their effect on the heart and lungs. This will also help us understand and study the short-term and long-term effects of SARS-COVID-19 (long COVID). Because it’s a new virus, there is so much unknown about its long-term effect on humans.

Secondary pulmonary hypertension: The role of PTEN (phosphatase and tensin homolog deleted on chromosome 10) in secondary pulmonary hypertension was first identified by Dr. Ravi and Dr. Sai-Sudhakar in collaboration with collaborators at The Ohio State University. PTEN is a key modulator of vascular remodeling of pulmonary vascular smooth muscle cells in pulmonary hypertension secondary to left heart failure. We use in-vitro and in-vivo rodent models to explore the role of PTEN as a potential therapeutic target.

Clinical Projects

Advanced heart failure: Of the more than 6 million American adults living with heart failure, about 10 percent have advanced heart failure. Their treatment decisions can become more complex. We’re developing quality education and expanding resources to rise above heart failure successfully. Heart transplantation and mechanical circulatory support are the treatment options for advanced heart failure.

Living with heart failure is a challenge. By analyzing large national and international clinical datasets, we aim to understand the quality of life factors, factors influencing survival, and causes of death.

Extracorporeal membrane oxygenation: In extracorporeal membrane oxygenation (ECMO), blood is pumped outside of your body to a heart-lung machine that removes carbon dioxide and sends oxygen-filled blood back to tissues in the body. Blood flows from the right side of the heart to the membrane oxygenator in the heart-lung machine and then is rewarmed and sent back to the body. This method allows the blood to "bypass" the heart and lungs, allowing these organs to rest and heal.

ECMO is used in critical care situations when your heart and lungs need help so that you can heal. It may be used in care for COVID-19, ARDS, and other infections.

The role and proper use of ECMO for acutely ill patients have not been definitively established. The continued evolution of ECMO technology also limits the conclusions that may be drawn from recent studies. The long-term effects of ECMO, especially potential neuropsychiatric effects, require further investigation. Finally, more detailed information about the cost of expanding the use of this therapy is needed to aid policymakers and health care providers. Hence, we are actively involved in analyzing clinical datasets to provide evidence for establishing better clinical guidelines, survival outcomes, and mortality indicators.